**4.7 Determination of creatinine and glomerular filtration rate as indices of renal function in goats**

Kidneys are responsible for water-electrolyte balance in the body, usually affected by activity-rest rhythm under hormonal influence. The diurnal changes are useful in chronobiology and chronopharmacology [80]. Many xenobiotics including antimicrobials are toxic to the kidney, and renal impairment can be assessed using creatinine clearance which is physiologically, pharmacologically and toxicologically related to body weight, clearance, volume of urine creatinine, plasma creatinine, serum creatinine, urine volume, glomerular filtration rate, creatinine clearance, creatinine half-life and depuration [81]. The plasma creatinine of Boer-Cross (0.60 mg/dl), Nubian (0.55 mg/dl) and Spanish (0.57 mg/dl) goat have been reported [82], whereas creatinine value (1.03–1.24 mg/dl) has been reported for healthy captive, Persian wild goat [83]. Area under curve could be used to determine creatinine clearance and plasma clearance as demonstrated in the equations given below [81].

$$\text{Dose (D)} = \text{AUC} \times [\text{CrCl} + \text{25}] \tag{30}$$

$$\text{Pcl} = \text{CrCl} + 25\tag{31}$$

$$\text{CrCl} = \text{Pcl-25} \tag{32}$$

$$\text{GFR} = \frac{14616.8}{\text{Crt1}/2} \tag{33}$$

$$\text{Depuration (Dep)} = \frac{\text{Ucr}}{\text{Pcr}} \tag{34}$$

$$\text{Serum creatinine} \left( \text{Scr} \right) = \frac{\text{Ucr}}{\text{1440}} \times 1000 \ (1000 \text{ ml} = 1 \text{ l}) \tag{35}$$

$$\text{Creatinine clearance (CrCl)} = \frac{\text{Ucr}}{\text{Pcr}} \times 144 \tag{36}$$

For example, paracetamol reduced glomerular filtration rate and induced less urinary excretion of isoniazid. Also, renal handling of isoniazid involved glomerular filtration, back diffusion and active tubular secretion [84]. Glomerular filtration rate which is a function of creatinine clearance can be affected by environmental and genetic factors as may be seen in native Pakistan goats administered ampicillin (20 mg/kg) with renal clearance of 0.08 ml/min/kg [85]. Hence, GFR is lower in Pakistan native than the foreign goats [86] unlike renal handling of marbofloxacin in Lohi sheep that involves both glomerular filtration and active tubular secretion [87] indicating that environment has physiological effects on various breeds of goats. This agrees with Bergmann's rule which states that light animals tend to live in hot regions of the world as opposed to fatty animals that tend to live in cold regions [88]. Since 8% of total body weight determines total blood volume, red cell volume and plasma volume could also be determined from hematocrit as indicated in the equation given below [89].

toxicological effects of antimicrobials in goats. Hence, several extrapolations are necessary in order to arrive at safe therapeutic and toxic doses [71]. The effective therapeutic doses of some antimicrobials translated from goats to human are given

Human equivalent dose HED ð Þ¼ animal dose � animal Km

whereas H = height, W = weight and K = constant.

height, respectively [72, 74].

*Goats (Capra) - From Ancient to Modern*

**4.5 Antimicrobial tissue residues in goats**

microorganisms against the antimicrobials.

**4.6 Antimicrobial resistance**

**148**

The formulas used for calculation of extrapolated doses are as follows [13, 72, 73].

Metabolism constant Km ð Þ¼ body surface area

But human body surface area BSA ð Þ¼ <sup>H</sup>0*:*<sup>528</sup> � <sup>W</sup>0*:*<sup>528</sup> � K (29)

But goat's BSA = WO.67 � <sup>10</sup>�<sup>3</sup> and dosimetric adjustment factor (DAF) is body weight of goat over body weight of humans and can be scaled up to 0.25, 0.33 and 0.58. However, body weight exponent of 0.67 and 10�<sup>3</sup> safety factor should be applied to goat, and the exponent of 0.528 should be applied to human weight and

Tissue residues of some antimicrobials above recommended thresholds are of public health importance. The presence of sulfadimidine residues (>0.1 ppm) in the liver, kidney, skeletal muscle, spleen, lung, brain and heart after administration of the drug (100 mg/kg) shows that the withdrawal period is longer than 30 days. Hence, sulfadimidine is not easily excreted in West African dwarf goats [13]. This may be due to the presence of desamino-sulfonamide, a sulfadimidine metabolite [75] which is eliminated slowly, thereby increasing the withdrawal time [76]. Lack of adequate water to dilute crystals of sulfadimidine in the kidney can lead to crystalluria that can consequently cause nephrosis in the affected animals [44], and consumptions of meats with high residues of sulfadimidine can cause Steven-Johnson syndrome in sensitive humans who may be slow or fast acetylators [13, 23]. Based on the tissue tolerance limit in cattle (5 ppm), the withdrawal period for tulathromycin is 19 days in cattle and 34 days in goat when administered subcutaneously [5]. The quantity of erythromycin residues (2.06 � 0.36 μg) is above the recommended threshold and may portend risk to public health. The bioavailability of tylosin in goat is 72.6� 2.3%, and its withdrawal period (48 h) [43] shows that the higher the bioavailability, the lower may be the withdrawal period in milk. Residues of antimicrobials in various tissues are presented in **Table 3**. A kid that feeds on milk with residues of antimicrobials may be vulnerable to resistance of

Goats are exposed to antimicrobials via prevention, treatment of diseases and growth promotion. This has caused the emergence of resistant *Salmonella*, *Campylobacter*, *Pasteurella*, *Actinobacillus*, *Enterococcus* and *Escherichia* species. The resistance is transferred by genes. But good and improved management practices and increased use of vaccines and probiotics could minimize emergence and spread of resistance genes [77].Off-label use of antimicrobials in goats could also contribute to emergence of resistance. Meanwhile, lack of official-generated data on consequences of extra-label use of drugs in goats cannot rule out its potential risks to goats

human Km (27)

body weight (28)

in **Table 2**.

Long-time administration of sulfadimidine over a period of 1 week may cause hemolysis leading to anemia [90]. Hence, the formula can be used to determine anemia and plasma deficit in goats, photos 1-46 [1, 2, 21, 22, 24].

**151**

*Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats*

*DOI: http://dx.doi.org/10.5772/intechopen.84551*

*Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats DOI: http://dx.doi.org/10.5772/intechopen.84551*

Total blood volume ¼ plasma � 100*=*100–hematocrit (37)

Long-time administration of sulfadimidine over a period of 1 week may cause hemolysis leading to anemia [90]. Hence, the formula can be used to determine

anemia and plasma deficit in goats, photos 1-46 [1, 2, 21, 22, 24].

*Goats (Capra) - From Ancient to Modern*

**150**

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1, Abergelle goat; 2, Afar goat; 3, African pygmy goat; 4, Altai mountain goat; 5, American Alpine doe; 6, Anglo Nubian goat; 7, Angora goat; 8, Ardi goats in the Arabian Peninsula; 9, Attappady black goat; 10, Babrbari-goat-breed; 11, Beetal-South Asia; 12, Black Bengal goat; 13, Black Oberhasli; 14, Bosque Valley Boer goats; 15, British primitive (Feral goat); 16, Dairy goat; 17, Dutch Toggenburger; 18, Eid-goat; 19, Indian Boer male goat; 20, Italian Adamello blond; 21, Kalahari-red-goat; 22, Marciano-Granadina; 23, Markhor wild goat; 24, Markhor-Pakistan; 25, Murciana goat; 26, Nederlandse Landgeit; 27, Nigeria West African dwarf goat; 28, Nubian blackgold goat; 29, Nubian-Ryan-Somma; 30, Oberhasli goats; 31, Osmanabadi goat; 32, Pakistan Bakra goat; 33, Paaltu Bakri-Nashik goat; 34, Shiba goat; 35, Pure-white-Tappra-teddy-male-goat; 36, Saanen-goat-in-Pakistan-Urdu; 37, Sangamneri-South Asia pro-poor; 38, Shatner goat; 39, Sirohi-male-kid-goat; 40, Sojat-goat; 41, Sokoto Red goat; 42, Teddy-tapra-bakra-goat; 43, Toggenburgerbok goat; 44, Toggenburg-Nigeriandwarf-Oberhasli-goat; 45, Valachian goat; 46, White Barbari-goat.
